Genetic Linkage and Association Analysis of COPD-Related Traits on Chromosome 8p

Figures & data

Table 1A DEFB1 polymorphisms genotyped in the Boston Early-Onset COPD Study. Assay details are available at http://www.innateimmunity.net/

rs#	IIPGA Identifier	Role	Allele frequency (founders)
rs5743402	IIPGA DEFB1 666	5′ genomic	0.22
rs2741136	IIPGA DEFB1 755	5′ genomic	0.28
rs2738182	IIPGA DEFB1 2181	5′ genomic	0.35
rs2702945	IIPGA DEFB1 3263	Intron	0.22
rs2738047	—	Exon, Val38Ile	0.005

*IIPGA = Innate Immunity Program for Genomic Applications.

Table 1B MSR1 polymorphisms genotyped in the Boston Early-Onset COPD Study. Assays were designed based on flanking sequences as per Xu et al. ([18])

Marker (names per Xu et al.)	rs#	Role	Allele frequency (founders)
PRO3 A > G	rs433235	Promoter	0.083
IVS5-59 C > A	—	Intron	0.049
P275A C > G	rs3747531	Exon, Pro275Ala	0.067
R293X C > T	—	Exon, Arg293X	0.029
INDEL7 3bp insertion-deletion	—	Intron	0.077

*By the extended pedigree family-based association test (PBAT): Moderate-to-severe airflow obstruction (FEV ₁ < 60% predicted, with FEV ₁/FVC < 90% predicted), post-bronchodilator: p = 0.01.

Mild-to-severe airflow obstruction (FEV ₁ < 80% predicted, with FEV ₁/FVC < 90% predicted), post-bronchodilator: p = 0.02.

Table 2 Chromosome 8p linkage analysis of post-bronchodilator FEV₁ and FEV₁/FVC in the Boston Early-Onset COPD Study. Maximum LOD scores are shown

Phenotype (post-bronchodilator)	Initial genome scan (Palmer et al., 2003)	Including additional markers	Smokers only, with additional markers
FEV1	3.30 (2 cM)	1.80 (1 cM)	0.35 (2 cM)
FEV1/FVC^†	0.46 (6 cM)	0.40 (0 cM)	0.03 (0 cM)

*Models adjusted for age, sex, height, pack-years, (pack-years)², race.

^†Models adjusted for age, pack-years, (pack-years)².

Table 3 DEFB1 haplotype analysis in the Boston Early-Onset COPD Study. Haplotypes with frequency ≥ 5% are shown. SNP identifiers are from Table 1A

DEFB1	DEFB1	DEFB1	DEFB1
666	755	2181	3263	Frequency	Phenotype
A	T	T	G	0.23	FEV1/FVC (pre-BD), p = 0.03
G	T	T	G	0.12	–
A	C	T	G	0.09	–
A	T	A	G	0.28	–
A	C	T	A	0.15	–

Table 4 MSR1 polymorphisms in the NETT-NAS case-control study. Marker names are from Table 1B

Marker	Allele frequency: cases	Allele frequency: controls
PRO3	0.083	0.082
IVS5-59	0.036	0.043
P275A	0.039	0.060
R293X	0.014	0.016
INDEL7	0.040	0.049

*p = 0.07 vs. controls (allele test).

Table 5 MSR1 haplotype analysis in the Boston Early-Onset COPD Study. Haplotypes with frequency ≥ 1% are shown. Marker names are from Table 1B

PRO3	IVS5-59	P275A	R293X	INDEL7	Frequency	Phenotype, post-BD
A	C	C	C	del	0.84	—
G	C	C	C	del	0.05	—
G	A	C	C	del	0.03	Mod-to-severe, p = 0.04
A	C	C	C	ins	0.01	—
A	C	G	C	ins	0.02	—

*Moderate-to-severe airflow obstruction: FEV₁ < 60% predicted, with FEV₁/FVC < 90% predicted.

Xu J, Zheng S L, Komiya A, Mychaleckyj J C, Isaacs S D, Chang B, Turner A R, Ewing C M, Wiley K E, Hawkins G A, Bleecker E R, Walsh P C, Meyers D A, Isaacs W B. Common sequence variants of the macrophage scavenger receptor 1 gene are associated with prostate cancer risk. Am J Hum Genet 2003; 72: 208–212, [INFOTRIEVE], [CROSSREF], [CSA]

 PubMed Web of Science ®Google Scholar